Abstract

BAFF (B-cell activating factor) is a recently identified member of TNF ligand superfamily that plays a critical role in B cell differentiation, survival, and regulation of immunoglobulin production. It exerts its effect by binding to three receptors: BAFF-R (BAFF receptor), TACI (transmembrane activator and CAML interactor), and BCMA (B-cell maturation antigen) which was known to be primarily expressed in B-lineage cells.

In this present study, we examined whether or not BAFF is also expressed in microglia and the synthesis and release of BAFF is regulated by stimuli. BAFF is expressed and released in primary rat microglia as well as BV-2 cells, mouse microglial cell line and the expression and release of BAFF is increased by Gmix-stimuli in microglia. The expression and release of BAFF is regulated by JAK-STAT, especially STAT1 and STAT3-dependent signaling pathway. Interestingly, SP600125, and SB203580, inhibitors of p38 and JNK, respectively, did not inhibit BAFF expression, but inhibit the release of BAFF by soluble form. It suggested that p38 and JNK signaling pathway regulate the release, not the synthesis of BAFF in microglia.

In BV-2 cells, only BAFF-R is expressed in cytoplasm and cell-surface. However, in primary rat microglia of microglia, BAFF-R and TACI are expressed in cytoplasm and cell-surface. Recombinant BAFF increases cytokines release, especially, IL-6 and IL-10 in primary rat microglia as well as BV-2 cells. It was suggested that BAFF, secreted by microglia may play important roles in CNS inflammation through regulating microglia as well as infiltrated B cells.